ii Dall'Implementazione del Regolamento (CE) n. 141/2000:

For a product to be granted OD it must also be demonstrated that "there is no satisfactory treatment for the condition in question in the El or, if there is, the product in question will be of significant benefit to patients affected by that condition." The EU Orphan Regulation thus requires a sponsor to provide details of "existing methods, which may include authorised medicinal products, medical devices or other methods of diagnosis, prevention or treatment, which are used in the Community [European Union]'.

Existing methods: Only authorised products should be taken into account. Non-pharmacological methods could be considered as a satisfactory method. In certain cases, 'magistral formulae' and 'officinal formulae', may be considered as satisfactory treatment if they are well known and safe and are in general practice in the EU iii Si riportano qui alcune definizioni sul Bisogno Clinico Insoddisfatto da parte di diverse autorità coinvolte:

A product can be said to provide significant benefit if it confers a clinically relevant advantage or offers a major contribution to patient care over existing authorized medicinal products or methods at the time of designation.

Unmet Medical Need - Definizioni, ranking et al.,

Una condizione il cui trattamento o diagnosi non è affrontata adeguatamente dalla terapia disponibile. Un bisogno medico insoddisfatto include un bisogno immediato di una popolazione definita (per es., per trattare una condizione grave con trattamento limitato o nullo) o un bisogno a lungo termine per la società (per es., per affrontare lo sviluppo della resistenza ai farmaci antibatterici).

No ranking

Setting: regolatorio USA

(Fonte: FDA Guidance for Industry. Expedited Programs for Serious Conditions Drugs and Biologics [FDA 2017a])

Una condizione per la quale non esiste un metodo soddisfacente di diagnosi, prevenzione o trattamento nell'UE o, anche se tale metodo esiste, in relazione alla quale il medicinale in questione sarà di grande vantaggio terapeutico per le persone colpite

No ranking

Setting: regolatorio UE

(Fonte: Article 4 paragraph 2 of Commission Regulation (EC) No. 507/2006 [about conditional marketing authorization])

Orphan Designation - A product is eligible if a sponsor can establish:

1. that it is intended for the diagnosis, prevention, or treatment of a life-threatening or chronically debilitating condition affecting not more than five in 10 thousand persons in the Community when the application is made, or

2. that it is intended for the diagnosis, prevention, or treatment of a life-threatening, seriously debilitating, or serious and chronic condition in the Community and that without incentives it is unlikely that the marketing of the medicinal product in the Community would generate sufficient return to justify the necessary investment AND,

3. That there exists no satisfactory method of diagnosis, prevention, or treatment of the condition in question that has been authorised in the Community or, if such method exists, that the medicinal product will be of significant benefit to those affected by that condition.

(Fonte: Designation criteria Art. 3 of Reg 141/2000)

Orphan condition: any deviation(s) from the normal structure or function of the body, as manifested by a characteristic set of signs and symptoms (typically a recognised distinct disease or a syndrome) that meets the criteria defined in Article 3 of Regulation (EC) No 141/2000

Orphan indication: the proposed indication for the purpose of orphan designation. This specifies if the medicinal product which is the subject of the designation application is intended for diagnosis, prevention, or treatment of the orphan condition.

Therapeutic indication: at the time of the orphan designation application, the sponsor proposes a therapeutic indication. The therapeutic indication granted at the time of marketing authorisation will be the result of the assessment of the quality, safety and efficacy data submitted with the marketing application and may be different from that initially proposed. The therapeutic indication can also be changed or expanded after MA on the basis of new clinical evidence.

(Fonte: Implementation of Reg 141/2000)

Il bisogno Terapeutico (valutato per singola indicazione terapeutica) è condizionato dalla disponibilità di terapie per la patologia in oggetto ed indica quanto l'introduzione di una nuova terapia sia necessaria per dare risposta alle esigenze terapeutiche di una popolazione di pazienti

Si ranking: Cinque livelli da Massimo a Scarso Setting: HTA/ payer nazionale Italia

(Fonte: Determinazione AIFA n. 1535/2017 sui criteri di classificazione dei farmaci innovativi e dei farmaci oncologici innovativi ai sensi dell'art. 1 comma 402 della legge 11 dicembre 2016, n. 232)

Approccio HTA

1. Elementi del Unmet Medical Need

2. Considerazioni degli stakeholder su Unmet Medical Need

3. Una proposta: prospettiva Population o Patient

4. Proposta per un approccio scaglionato alla valutazione di HT basato su UMN da parte dei decisori. Gli elementi considerati non sono esaustivi e dipendono dal decisore. Tre categorie tra cui l'adeguatezza dei trattamenti alternativi, il carico di malattia o la dimensione della popolazione